The nitric acid esters of organic compounds, commonly known as nitrated organic compounds, are known and have been used as vasodilating agents for some time. Among these, the usefulness of mono and di-nitrated, isosorbide is well known, and furthermore, compounds with vascular and coronary activities based on substitution reactions on the free hydroxyl group of isosorbide mononitrate have been described. For example, U.S. Pat. No. 4,891,373 patent describes aminepropanol derivatives for the treatment of angina pectoris and systemic and pulmonary hypertension.
U.S. Pat. No. 5,665,766 patent describes isosorbide 5-mononitrate 2-acetylsalicylate as well as its platelets anti-aggregating activity.
One of the main problems of the above-mentioned nitrated organic compounds resides on the fact that these are quite sensitive in relation to the phenomena known as tachyphylaxy or tolerance, which consists in that the organism's response with respect to its effect decreases during prolonged treatment, and it is then required to sensitively and gradually increase the administered doses or otherwise perform a pharmacological wash-out.
It is also known that one way of reducing the tolerance of the nitrated organic compounds consists in introducing thiol groups in the molecule, for example by using sulphur containing amino acids. Thus, European patent EP-B-0362575 describes nitrated organic compounds with incorporated cysteine and, mainly, methionine molecules.
Patent application WO-A-92/04337 describes organic nitrated derivatives of the thiazolidine ring with vasodilating activity and a reduced tolerance.
Patent application WO-A-93/03037 describes an enormous amount of different nitrated organic vasodilating compounds, with reduced tolerance, of highly variable structures.
Patent application WO-A-00/20420 describes isosorbide mononitrates wherein the free hydroxyl group is esterified with either carboxylic acids or with thioacids wherein said ester groups are in trans position with respect to the nitrate group.
Finally, patent application WO-A1-2005/037842 describes isosorbide mononitrates wherein the free hydroxyl group has been replaced by a wide range of substituents.
The compounds described in the art however, are not fully satisfactory as they have a limited duration of action.
It has now been surprisingly found that certain compounds, some of which were claimed but not disclosed in patent application WO-A1-2005/037842, have not only high antithrombotic and vasodilatatory activities, but also a longer duration of action than their structural homologues described in said patent application.